Endocannabinoids in the brain are essential for regulating food consumption and energy expenditure. Researchers suggest that adjusting the function of these molecules may aid in addressing obesity issues.
Endocannabinoids in the brain are crucial for controlling food intake and energy expenditure. Researchers at Université de Montréal’s affiliated hospital research center (CRCHUM) believe that modifying the behavior of these molecules could assist in combating obesity.
For several years, Stephanie Fulton, a medical professor at Université de Montréal, and her research team have been exploring how the human nervous system influences eating behavior and physical activity, as well as how metabolism impacts mood.
Their most recent findings, published in Nature Communications, build on their previous research.
In their investigation, the primary authors, David Lau, a doctoral student at Université de Montréal, and Stephanie Tobin, a former postdoctoral fellow, discovered that weight management in mice is significantly influenced by neurons located in the nucleus accumbens. This area of the brain is abundant in endocannabinoids and plays a vital role in food reward processing and regulating physical activity.
Within the brain, the enzyme ABHD6 breaks down an essential endocannabinoid known as 2-arachidonoylglycerol (2-AG).
After a 2016 discovery by a team led by Marc Prentki at CRCHUM that inhibiting ABHD6 throughout the body led to reduced body weight and protection against diabetes, the researchers sought to understand what role this enzyme plays in the brain concerning appetite and weight management.
“We initially thought that raising 2-AG levels would encourage eating by boosting cannabinoid signals. However, we surprisingly found that when we removed the ABHD6 gene in the nucleus accumbens of mice, they showed less desire for food and more inclination towards physical activity,” Fulton explained.
“The experimental mice opted to spend more time on a running wheel compared to the control group, which became overweight and sluggish.”
By administering a precise ABHD6 inhibitor directly into the brains of mice, her team successfully prevented weight gain and obesity.
Can produce differing outcomes
Identifying specific neuronal routes in the brain for weight control is vital for contemporary scientists. Depending on which brain region is targeted, inhibiting ABHD6 can yield contrasting outcomes.
In a 2016 study, Fulton and colleague Thierry Alquier discovered that obstructing ABHD6 in certain hypothalamic neurons led to weight loss resistance in mice.
Conversely, in the current research, they demonstrate that broadly inhibiting this molecule across the brain results in decreased weight gain when on a high-fat diet.
No signs of anxiety
“We also found that mice with the ABHD6 gene inhibition did not exhibit signs of anxiety or depressive behaviors,” said Fulton.
This finding is significant because Rimonabant, a weight-loss medication that targeted cannabinoid receptors in the central nervous system, was withdrawn from the market in the late 2000s due to patients reporting severe side effects, including depression and suicidal thoughts.
Fulton’s team’s recent research is laying the groundwork for new treatments to combat obesity and metabolic diseases like type 2 diabetes, according to the scientists.
While drug inhibitors for ABHD6 are under assessment, it remains uncertain if the mechanisms that were effective in mice will apply to human subjects.
